The activity of pharmaceutical compounds is modulated, in part, by their metabolic inactivation and elimination. As a result, understanding the metabolic pathways associated with the inactivation and elimination of a compound provides valuable information about the pharmacokinetics of the compound. Generally speaking, metabolism of a compound comprises two phases. Phase I reactions usually precede Phase II, though not necessarily. During phase I reactions, polar bodies are either introduced or unmasked, which results in (more) polar metabolites of the original compound. During phase II reactions, a watersoluble moiety is conjugated to a polar body introduced or unmasked during phase I.
Phase II may involve UDP-glucuronosyltransferases (UGTs), which are extensively involved in the overall metabolism and disposition of endo- and xenobiotics. UGTs catalyze the transfer of the glucuronosyl group from uridine 5′-diphospho-glucuronic acid (UDP-glucuronic acid) to substrate molecules that contain oxygen, nitrogen, sulfur or carboxyl functional groups. Glucuronidation of a compound may modulate the bioavailability, activity, and clearance rate of a compound.
As a result, there is a need in the art to identify phase II metabolic compounds. Additionally, there is a need for methods of detecting, quantifying, and manipulating the production of these compounds.